1. Field of the Invention
The present invention relates to the acylation or alkylation of aromatic compounds in hydrogen fluoride, wherein the acylated or alkylated product is soluble in hydrogen fluoride but the aromatic compound is sufficiently insoluble in hydrogen fluoride that a two phase reaction medium forms. The present invention particularly relates to a continuous multistage process for carrying out the acylation or alkylation of aromatic compounds in hydrogen fluoride.
2. Description of Related Art
The following information is disclosed in accordance with the terms of 37 CFR 1.56, 1.97 and 1.98.
U.S. Pat. No. 3,385,886, shows the production of phenylalkane derivatives such as ibuprofen in which the first step of the process is the reaction of phenylalkane with acetyl chloride in the presence of aluminum chloride to produce an alkylphenylacetophenone.
Japanese Patent Publication (Early Disclosure) No. 60 [1985]188,343, discloses the preparation of p-isobutylacetophenone by the acetylation of isobutylbenzene using an acetylating agent acetyl fluoride prepared by reacting acetic anhydride with hydrogen fluoride, and as a catalyst, a combination of hydrogen fluoride and boron trifluoride.
Baddely et al., Journal of the Chemical Society, 4943-4945 [1956], discloses on page 4945 the preparation of 4'-isobutylacetophenone by the Friedel-Crafts acetylation of isobutylbenzene with acetyl chloride using aluminum chloride as a catalyst.
U.S. Pat. No. 4,981,995, issued Jan. 1, 1991 to Elango et al., shows the production of 4'-isobutylacetophenone (IBAP) by the Friedel-Crafts acetylation of isobutylbenzene (IBB) with an acetylating agent which may be acetyl fluoride (AcF) or acetic anhydride (Ac.sub.2 O), using a catalyst which may be hydrogen fluoride. The 4'-isobutylacetophenone is disclosed as an intermediate in a process for the production of ibuprofen.
U.S. Pat. No. 4,990,681 issued Feb. 5, 1991, discloses the operation of an extractor-reactor to produce IBAP and the removal of HF from the IBAP product by reacting the HF with acetic anhydride in an HF removal column, both contemplated to be used in combination with the process of the present invention. The entire disclosure of U.S. Pat. No. 4,990,681 is hereby incorporated by reference herein.
The acylation or alkylation of aromatic compounds in hydrogen fluoride is well known in the art. Since, typically, the aromatic compound reactant has a limited solubility in hydrogen fluoride, whereby the contact between the aromatic compound and the acylating or alkylating agent is restricted, the rate of the reaction is reduced. In the past, due to the reduced rate of reaction, the acylation or alkylation of aromatic compounds in hydrogen fluoride was carried out in a batch mode, typically in a continuously stirred batch reactor.
Examples of aromatic compounds which form a separate and distinct phase with hydrogen fluoride are described in Dolkady Akademii Nauk USSR, 95(2), 297-299 (1954) and Zhurnal Fizicheskoi Khimii, 31, 1377-1386 (1957). Aromatics sparingly soluble in hydrogen fluoride (approximately one (1)% by weight or less) include naphthalene, phanthrene, diphenylmethane, triphenylmethane, chlorobenzene, tetralin, 2-methylnaphthalene, and diphenyl. Many aromatics, especially those with--H or--alkyl substitution are often sparingly soluble in hydrogen fluoride. Thus, one skilled in the art can understand the broad applicability and considerable value of a reaction technique which would permit the continuous acylation or alkylation of aromatic compounds in hydrogen fluoride.